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Three new cobalt(II) complexes, [Co(MQL)

The certainty with which people hold their attitudes is an important consideration because attitudes held with certainty better predict judgment and behavior than attitudes held with doubt. However, little is known about whether people's assessments of their certainty reflect a disposition to hold attitudes with confidence. Adapting methods used to document individual differences in people's attitudes, the present research demonstrates that the certainty with which people hold any given attitude is in part a reflection of a relatively stable disposition. Across 5 studies and 6 samples (total N = 106,050), we demonstrate dispositional variability in attitude certainty and show that it is related to but distinct from confidence in other judgmental domains. We also demonstrate that dispositional attitude certainty may be useful in predicting certainty in newly formed evaluations (Study 3) and an important consequence of certainty-attitude-behavior correspondence (as indicated by reports of behavioral intentions and recent behavior; Study 4 and Student Sample in Study 5). Furthermore, we demonstrate that dispositional attitude certainty is relatively stable over time (Study 5). Results are discussed with respect to potential mechanisms and boundary conditions relating to dispositional attitude certainty, the implications of these individual differences for attitudes and persuasion, as well as the potential origins of dispositional attitude certainty. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Bombesin receptor subtype-3(BRS-3) is an orphan receptor in the bombesin receptor family. Its signal transduction mechanism and biological function have attracted much attention. Seeking the ligand for BRS-3 is of great significance for exploring its function. Considering the fact that the activation of BRS-3 receptor can induce the change in intracellular Ca~(2+) concentration, the fluo-rometric imaging plate reader(FLIPR) was utilized for ligand screening at the cellular level. Among more than 400 monomeric compounds isolated from Chinese herbs, yuanhunine from Corydalis Rhizoma and sophoraisoflavanone A and licoriphenone from Glycyrrhizae Radix et Rhizoma antagonized BRS-3 to varying degrees. It was confirmed in HEK293 cells expressing BRS-3 that yuanhunine, sophoraisoflavanone A, and licoriphenone inhibited the calcium current response after the activation of BRS-3 by [D-Phe~6,β-Ala~(11),Phe~(13),Nle~(14)]bombesin-(6-14) in a dose-dependent manner with the IC_(50) values being 8.58, 4.10, and 2.04 μmol·L~(-1), respectively. Further study indicated that yuanhunine and sophoraisoflavanone A exhibited good selectivity for BRS-3. In this study, it was found for the first time that monomers derived from Chinese herbs had antagonistic activity against orphan receptor BRS-3, which has provided a tool for further study of BRS-3 and also the potential lead compounds for new drug discovery. At the same time, it provides reference for the research and development of innovative drugs based on the active ingredients of Chinese herbs.

It is high of the incidence of stroke and dementia with the advent of an aging society. Post-stroke cognitive impairment is one of the common complications of stroke, which not only seriously affects the life quality of patients, but also significantly reduces the survival time of stroke patients. Moreover, it also brings in heavy burden to the family and society. The development of vascular dementia could be reduced by early intervention after stroke. Management of vascular risk factors could be an effective way to prevent dementia. This study aimed to investigate the plasma biochemical parameters of post-stroke cognitive impairment (PSCI) and its potential risk factors.Four hundred eighty-seven consecutive patients with ischaemic stroke were included and followed up for 3 years. Among these patients, 132 cases were diagnosed as PSCI. The cognitive impairment of patients with PSCI was assessed by the Mini Mental State Examination and Montreal cognitive assessment scale. The plasma biochemical parameters and blood coagulation, as well as computed tomography and magnetic resonance imaging of all the patients after admission, were measured.Multivariate analyses revealed that increased age, carotid plaque, cerebral atrophy, white matter lesions (WML), alcohol use, smoking and history of systolic blood pressure ≥170 mmHg was highly associated with PSCI (P0.05). Elevated homocysteine, low-density lipoprotein (LDL), and uric acid were also highly associated with PSCI. Logistic regression analysis identified five risk factors correlated with PSCI including alcohol use [odds ratio (OR): 5.138, 95% confidence interval (CI): 1.014-26.04, P=0.048], history of high systolic blood pressure (OR: 12.171, 95% CI: 3.339-44.363, P=0.001), carotid plaque (OR: 1.692, 95% CI: 1.032-2.796, P=0.040), cerebral atrophy (OR: 2.280, 95% CI: 1.294-4.001, P=0.004), and WML (OR: 3.155, 95% CI: 1.868-5.324, P=0.001). Three plasma biochemical parameters were also associated with PSCI including homocysteine (OR: 1.018, 95% CI: 0.944-1.042, P=0.010), and LDL (OR: 0.83, 95% CI: 0.6-1.148, P=0.051), and uric acid (OR: 1.00, 95% CI: 0.998-1.002, P=0.007). The area under the receiver operating curve for the risk factors of PSCI was 0.821 with the sensitivity of 76.3% and specificity of 71.9%.Elevated homocysteine, LDL, and uric acid were highly related to PSCI, which may help predict PSCI. These plasma biochemical parameters together with vascular risk factors, may improve the sensitivity for early detection of PSCI.

Lung cancer is the most common malignancy and the leading cause of cancer death worldwide, and lung adenocarcinoma (LUAD) is the most prevalent subtype. Considering the emergence of resistance to therapies, it is urgent to develop more effective therapies to improve the prognosis. Here we reported that pancreatic progenitor cell differentiation and proliferation factor (PPDPF) deficiency inhibited LUAD development both in vitro and in vivo. Mechanistically, PPDPF induces hyperactive STAT3 by interfering STAT3-PTPN1 interaction. Activated STAT3 promoted BMPR2 transcription, which further inhibited apoptosis. Moreover, PPDPF reduced NK cell infiltration and activation to develop an immunosuppressive microenvironment, which was also mediated by STAT3. Furthermore, we identified that the expression of PPDPF was positively correlated with the malignant features of LUAD, as well as BMPR2 and p-STAT3 level in clinical samples. Therefore, our study suggests that PPDPF positively regulates BMPR2 expression and facilitates immune escape via regulating STAT3 activity, providing a potential therapy target for LUAD.

Hepatocellular carcinoma (HCC) is a highly heterogeneous solid tumor with high morbidity and mortality. AT-rich interaction domain 1A (ARID1A) accounts for up to 10% of mutations in liver cancer, however, its role in HCC remains controversial, and no targeted therapy has been established.The expression of ARID1A in clinical samples was examined by Western blot and immunohistochemical staining. ARID1A was knocked out by Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) in HCC cell lines, and the effects of glucose deprivation on cell viability, proliferation, and apoptosis were measured. Mass spectrometry analysis was used to find ARID1A-interacting proteins, and the result was verified by co-immunoprecipitation and Glutathione S Transferase (GST) pull-down. The regulation of ARID1A target gene USP9X was investigated by chromatin immunoprecipitation, Glutathione S Transferase (GST) pull-down, luciferase reporter assay, and so forth. Finally, drug treatments were performed to explore the therapeutic potential of the agents targeting ARID1A-deficient HCC in vitro and in vivo.Our study has shown that ARID1A loss protected cells from glucose deprivation-induced cell death. A mechanism study disclosed that AIRD1A recruited histone deacetylase 1 via its C-terminal region DUF3518 to the promoter of USP9X, resulting in down-regulation of USP9X and its target protein kinase AMP-activated catalytic subunit α2 (PRKAA2). ARID1A knockout and a 1989∗ truncation mutant in HCC abolished this effect, increased the levels of H3K9 and H3K27 acetylation at the USP9X promoter, and up-regulated the expression of USP9X and protein kinase AMP-activated catalytic subunit α2 (PRKAA2), which mediated the adaptation of tumor cells to glucose starvation. Compound C dramatically inhibited the growth of ARID1A-deficient tumors and prolongs the survival of tumor-bearing mice.HCC patients with ARID1A mutation may benefit from synthetic lethal therapy targeting the ubiquitin-specific peptidase 9 X-linked (USP9X)-adenosine 5'-monophosphate-activated protein kinase (AMPK) axis.

Purpose Breast cancer (BC) is one of the most common malignant tumors, affecting a significant number of women worldwide. MicroRNAs (miRNAs) have been reported to play important roles in tumorigenesis. The aim of this study was to determine the roles of miR-182-5p in BC progression. Materials and methods The expressions of miR-182-5p and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) were measured in BC tissues and cells by quantitative real-time polymerase chain reaction or Western blot. Cell proliferation and invasion were detected by cell counting kit-8 assay and trans-well assay, respectively. The interaction between miR-182-5p and PTEN was probed by bioinformatics analysis, luciferase activity, and RNA immunoprecipitation. A murine xenograft model was established to investigate the role of miR-182-5p in BC progression in vivo. Results An abundance of miR-182-5p was noted in BC tissues and cells. High expression of miR-182-5p was associated with poor survival. Abrogation of miR-182-5p inhibited cell proliferation and invasion in BC cells. Interestingly, PTEN was indicated as a target of miR-182-5p, and its restoration reversed miR-182-5p-mediated promotion of proliferation and invasion of BC cells. Moreover, depletion of miR-182-5p suppressed tumor growth via up-regulating PTEN expression in the murine xenograft model. Conclusion MiR-182-5p exhaustion blocked cell proliferation and invasion by regulating PTEN expression, providing a novel therapeutic avenue for treatment of BC.

Objective To evaluate the effect of methylprednisolone sodium succinate combined with tropisetron on postoperative nausea and vomiting(PONV)under microvascular decompression of hemifacial spasm.Methods From January to June 2019,485 patients undergoing microvascular decompression for facial spasm at Department of Neurosurgery,Peking University People's Hospital were randomly assigned into two groups with random number table method.For group A(n=242),2 ml saline was administrated by intravenous drip before induction and 5 mg tropisetron after operation.For group B(n=243),40 mg methylprednisolone sodium succinate was administrated by intravenous drip before induction and 5 mg tropisetron after operation.The anesthesia time,operation time,and incidence of PONV in 0-24 h and 24-48 h were recorded for the comparison of the remedial treatment rate of nausea and vomiting between the two groups.Results There was no significant difference in age,gender,smoking history,body mass index value,American Society of Anesthesiologists score,medical history,surgical side,PONV history,operation time or anesthesia time between the two groups(all P0.05).The incidence of PONV in group A was 35.5% and 18.2% during 0-24 h and 24-48 h,respectively,which was significantly higher than that(18.5%,χ

Background Emerging evidence indicates nitrite inhalants have become increasingly prevalent among men who have sex with men (MSM). The present study aimed to describe the prevalence and correlates of nitrite inhalants use and its association with risky sexual behaviors and human immunodeficiency virus (HIV)/syphilis infection among MSM in Chongqing, a city in China where MSM were burdened with the highest pooled HIV prevalence in the country. Methods This cross-sectional study was conducted in Chongqing between March 2019 and February 2020. Information of demographics, drug use, sexual behaviors and HIV testing was collected through an anonymous survey. Blood samples were drawn from each participant for the diagnoses of HIV and syphilis. Logistic regression analysis was performed to evaluate factors correlated with nitrite inhalants use and its relationship with risky sexual behaviors and HIV/syphilis infection. Results Of the 1151 eligible participants, 18.9% (218) reported use of at least one type of recreational drugs in the past 6 months, and nitrite inhalants were the most commonly used substance (17.7, 95% confidence interval [CI]: 15.6–20.2%). The proportions of participants reported engaging in group sex and practicing condomless internal ejaculation during anal sex in the past six months were 5.8% (95% CI: 4.4–7.2%) and 41.7% (95% CI: 38.7–44.7%), respectively. The general prevalence of HIV and syphilis infection among the enrolled MSM were 16.8% (95% CI: 14.7–19.0%) and 12.6% (95% CI: 10.7–14.4%), respectively. Factors positively associated with nitrite inhalants use included: age ≤ 25 (adjusted odds ratio [aOR] = 2.08, 95% CI: 1.10–3.94), monthly individual income ≥ CNY 3000 (Chinese Yuan) (aOR = 1.95, 95% CI: 1.18–3.22), preferring receptive anal intercourse (aOR = 2.27, 95% CI: 1.34–3.84) and versatile anal intercourse (aOR = 2.60, 95% CI: 1.64–4.13), age at first anal intercourse OR = 1.79, 95% CI: 1.21–2.67), engaging in group sex in the past six months (aOR = 9.34, 95% CI: 4.95–17.63), having multiple male sex partners in the past 6 months (aOR = 2.32, 95% CI: 1.50–3.58), practicing CIE during anal sex in the past six months (aOR = 1.71, 95% CI: 1.19–2.46), HIV infection (aOR = 1.72, 95% CI: 1.11–2.66) and syphilis infection (aOR = 1.98, 95% CI: 1.23–3.17). Conclusions This study found that nitrite inhalants were the most commonly used recreational substance among MSM and nitrite inhalants use were associated with higher probability of HIV and syphilis infection. Therefore, increased attention and counselling should be given to nitrite inhalants-using MSM.

Non-alcoholic fatty liver disease (NAFLD) has become the most prevalent chronic liver disease in the world, however, no drug treatment has been approved for this disease. Thus, it is urgent to find effective therapeutic targets for clinical intervention. In this study, we find that liver-specific knockout of PPDPF (PPDPF-LKO) leads to spontaneous fatty liver formation in a mouse model at 32 weeks of age on chow diets, which is enhanced by HFD. Mechanistic study reveals that PPDPF negatively regulates mTORC1-S6K-SREBP1 signaling. PPDPF interferes with the interaction between Raptor and CUL4B-DDB1, an E3 ligase complex, which prevents ubiquitination and activation of Raptor. Accordingly, liver-specific PPDPF overexpression effectively inhibits HFD-induced mTOR signaling activation and hepatic steatosis in mice. These results suggest that PPDPF is a regulator of mTORC1 signaling in lipid metabolism, and may be a potential therapeutic candidate for NAFLD., Non-alcoholic fatty liver disease (NAFLD) has become a prevalent chronic liver disease, however, drugs to treat this disease are still lacking. Here, the authors show that PPDPF inhibits the development of hepatic steatosis by negatively regulating mTORC1-S6K-SREBP1 signaling, which provides a potential therapeutic candidate for NAFLD treatment.

Ultrasensitive detection of specific biomarkers in clinical serum is helpful for early diagnosis of cervical cancer. In this paper, a surface-enhanced Raman scattering (SERS)-based immunoassay was developed for the simultaneous determination of squamous cell carcinoma antigen (SCCA) and osteopontin (OPN) in cervical cancer serum. Au-Ag nanoshuttles (Au-AgNSs) as SERS tags and hydrophobic filter paper-based Au nanoflowers (AuNFs) as capture substrate were constructed into a sandwich structure which served as an ultrasensitive SERS-based immunoassay platform. Finite difference time domain simulation confirmed that the electromagnetic field coupled between the AuNFs had a prominent SERS signal enhancement effect, which improved the detection sensitivity. SERS mapping showed that hexadecenyl succinic anhydride hydrophobic treatment could prevent the analyte from being quickly absorbed by the filter paper and increase the retention time to be more evenly distributed on the filter paper substrate. The immunoassay platform was verified to have good selectivity and reproducibility. With this method, the detection limits of SCCA and OPN in human serum were as low as 8.628 pg/mL and 4.388 pg/mL, respectively. Finally, in order to verify the feasibility of its clinical application, the serum samples of healthy subjects; cervical intraepithelial neoplasia I (CINI), CINII, and CINIII; and cervical cancer patients were analyzed, and the reliability of the results was confirmed by enzyme-linked immunosorbent assay experiments. The constructed SERS-based immunoassay platform could be used as a clinical tool for early screening of cancers in the future.

Autotaxin (ATX) is considered as an interesting drug target for the therapy of several diseases. The goal of the research was to detect new ATX inhibitors which have novel scaffolds by using virtual screening. First, based on two diverse receptor-ligand complexes, 14 pharmacophore models were developed, and the 14 models were verified through a big test database. Those pharmacophore models were utilized to accomplish virtual screening. Next, for the purpose of predicting the probable binding poses of compounds and then carrying out further virtual screening, docking-based virtual screening was performed. Moreover, an excellent 3D QSAR model was established, and 3D QSAR-based virtual screening was applied for predicting the activity values of compounds which got through the above two-round screenings. A correlation coefficient r2, which equals 0.988, was supplied by the 3D QSAR model for the training set, and the correlation coefficient r2 equaling 0.808 for the test set means that the developed 3D QSAR model is an excellent model. After the filtering was done by the combinatory virtual screening, which is based on the pharmacophore modelling, docking study, and 3D QSAR modelling, we chose nine potent inhibitors with novel scaffolds finally. Furthermore, two potent compounds have been particularly discussed.

Background and Aims Magnetically controlled capsule endoscopy (MCE) has become an efficient diagnostic modality for gastric diseases. We developed a novel automatic gastric lesion detection system to assist in diagnosis and reduce inter-physician variations. This study aimed to evaluate the diagnostic capability of the computer-aided detection system for MCE images. Methods We developed a novel automatic gastric lesion detection system based on a convolutional neural network (CNN) and faster region-based convolutional neural network (RCNN). A total of 1,023,955 MCE images from 797 patients were used to train and test the system. These images were divided into 7 categories (erosion, polyp, ulcer, submucosal tumor, xanthoma, normal mucosa, and invalid images). The primary endpoint was the sensitivity of the system. Results The system detected gastric focal lesions with 96.2% sensitivity (95% confidence interval [CI], 95.7%-96.5%), 76.2% specificity (95% CI, 75.97%-76.3%), 16.0% positive predictive value (95% CI, 15.7%-16.3%), 99.7% negative predictive value (95% CI, 99.74%-99.79%), and 77.1% accuracy (95% CI, 76.9%-77.3%) (sensitivity was 99.3% for erosions; 96.5% for polyps; 89.3% for ulcers; 87.2% for submucosal tumors; 90.6% for xanthomas; 67.8% for normal; and 96.1% for invalid images). Analysis of the receiver operating characteristic curve showed that the area under the curve for all positive images was 0.84. Image processing time was 44 milliseconds per image for the system and 0.38 ± 0.29 seconds per image for clinicians (P Conclusions The CNN faster-RCNN-based diagnostic program system showed good performance in diagnosing gastric focal lesions in MCE images.

Background Cancer cachexia is a serious metabolic disorder syndrome that is responsible for the deaths of approximately 30% of patients with cancer, but effective drugs for cancer cachexia are still lacking. Inflammatory cytokines such as TNF-α or IL-6 are involved in the induction of skeletal muscle atrophy and fat depletion in patients with cancer cachexia. Purpose In this study, we assessed the therapeutic effects of the natural compound alantolactone (AL) on cancer cachexia and tried to clarify the mechanisms by which it ameliorates muscle atrophy. Methods The C26 tumor-bearing cancer cachexia mouse model was used to evaluate the efficacy of AL in alleviating cancer cachexia in vivo. The levels of IL-6 or TNF-α in mouse serum were detected using ELISA kits. Cultured C2C12 myotubes and 3T3-L1 adipocytes treated with conditioned medium of C26 tumor cells, IL-6 or TNF-α were employed as in vitro cancer cachexia models to examine the effects of AL in vitro. Results AL (5 or 10 mg/kg, qd, i.p.) protected mice with C26 tumors and cachexia from a loss of body weight and muscle wasting but only slightly ameliorated fat loss. The circulating level of IL-6 but not TNF-α was significantly decreased by AL. AL treatment significantly inhibited STAT3 activation in the gastrocnemius (GAS) muscle of cancer cachexia mice. AL (0.125, 0.25, 0.5 and 1 µM) dose-dependently ameliorated myotube atrophy and STAT3 activation in cultured C2C12 myotubes induced by conditioned medium from C26 tumor cells. AL also ameliorated C2C12 myotube atrophy induced by IL-6 and inhibited IL-6-mediated STAT3 activation. AL exhibited weak effects on ameliorating TNF-α-mediated myotube atrophy and NF-κB activation. Only AL at high doses of more than 5 µM ameliorated lipolysis and STAT3 activation induced in mature 3T3-L1 adipocytes by conditioned medium from C26 tumor cells. Conclusions AL significantly ameliorated muscle atrophy in a cancer cachexia model mainly through the inhibition of the STAT3 pathway. AL might be a promising lead compound in the development of drug candidates for cancer cachexia therapy.

Ochratoxin A(OTA) is considered to be one of the most important contaminants of food and feed worldwide. The liver is one of key target organs for OTA to exert its toxic effects. Due to current lifestyle and diet, nonalcoholic fatty liver disease (NAFLD) has been the most common liver disease. To examine the potential effect of OTA on hepatic lipid metabolism and NAFLD, C57BL/6 male mice received 1 mg/kg OTA by gavage daily. Compared with controls, OTA increased lipid deposition and TG accumulation in mouse livers. In vitro OTA treatment also promoted lipid droplets accumulation in primary hepatocytes and HepG2 cells. Mechanistically, OTA prevented PPARγ degradation by reducing the interaction between PPARγ and its E3 ligase SIAH2, which led to activation of PPARγ signaling pathway. Furthermore, downregulation or inhibition of CD36, a known of PPARγ, alleviated OTA-induced lipid droplets deposition and TG accumulation. Therefore, OTA induces hepatic steatosis via PPARγ-CD36 axis, suggesting that OTA has an impact on liver lipid metabolism and may contribute to the development of metabolic diseases.

In the face of the worldwide threat of severe acute respiratory syndrome (SARS) to human life, some of the most urgent challenges are to develop fast and accurate analytical methods for early diagnosis of this disease as well as to create a safe anti-viral vaccine for prevention. To these ends, we investigated the antigenicity of the spike protein (S protein), a major structural protein in the SARS-coronavirus (SARS-CoV). Based upon the theoretical analysis for hydrophobicity of the S protein, 18 peptides were synthesized. Using Enzyme-Linked Immunosorbent Assay (ELISA), these peptides were screened in the sera from SARS patients. According to these results, two fragments of the S gene were amplified by PCR and cloned into pET-32a. Both S fragments were expressed in the BL-21 strain and further purified with an affinity chromatography. These recombinant S fragments were confirmed to have positive cross-reactions with SARS sera, either by Western blot or by ELISA. Our results demonstrated that the potential epitope regions were located at Codons 469–882 in the S protein, and one epitope site was located at Codons 599–620. Identification of antigenic regions in the SARS-CoV S protein may be important for the functional studies of this virus or the development of clinical diagnosis.

Retinoid X receptor alpha (RXRα), a nuclear receptor of transcription factor, controls various physiological and pathological pathways including cellular growth, proliferation, differentiation, and apoptosis. Here, we report that RXRα is phosphorylated at its N-terminal A/B domain by cyclin-dependent kinase 1 (Cdk1) at the onset of mitosis, triggering its translocation to the centrosome, where phosphorylated-RXRα (p-RXRα) interacts with polo-like kinase 1 (PLK1) through its N-terminal A/B domain by a unique mechanism. The interaction promotes PLK1 activation, centrosome maturation, and mitotic progression. Levels of p-RXRα are abnormally elevated in cancer cell lines, during carcinogenesis in animals, and in clinical tumor tissues. An RXRα ligand XS060, which specifically inhibits p-RXRα/PLK1 interaction but not RXRα heterodimerization, promotes mitotic arrest and catastrophe in a tumor-specific manner. These findings unravel a transcription-independent action of RXRα at the centrosome during mitosis and identify p-RXRα as a tumor-specific vulnerability for developing mitotic drugs with improved therapeutic index.

Malaria parasite strains have emerged to tolerate the therapeutic effects of the prophylactics and drugs presently available. Recent studies have shown that KAI715 and its analogs inhibit malaria parasites growth by binding to lipid kinase PI(4)K (phosphatidylinositol-4-OH kinase) of the parasites. Therefore, targeting PI(4)K may open up new avenues of target-based drug discovery to identify novel anti-malaria drugs. In this investigation, we describe the discovery of novel potent PfPI(4)K (PI(4)K from P. falciparum) inhibitors by employing a proposed hybrid virtual screening (VS) method, including pharmacophore model, drug-likeness prediction and molecular docking approach. 3D structure of PfPI(4)K has been established by homology modeling. Pharmacophore model HypoA of PfPI(4)K inhibitors has been developed based on the ligand complexed with its corresponding receptor. 174 compounds with good ADMET properties were carefully selected by a hybrid virtual screening method. Finally, the 174 hits were further validated by using a new pharmacophore model HypoB built based on the docking pose of BQR685, and 95 compounds passed the last filter. These compounds would be further evaluated by biological activity assays. The molecular interactions of the top two potential inhibitors with the active site residues are discussed in detail. These identified hits can be further used for designing the more potent inhibitors against PfPI(4)K by scaffold hopping, and deserve consideration for further structure-activity relationship (SAR) studies.

Human testis-specific and bromodomain-containing protein (hBRDT) is essential for chromatin remodeling during spermatogenesis and is therefore an attractive target for the discovery of male contraceptive drugs. In this study, pharmacophore modeling was carried out based on the crystal structure of hBRDT in complex with the inhibitor, JQ1. The established pharmacophore model was used as a 3D search query to identify potent hBRDT inhibitors from an in-house chemical database. A molecular docking analysis was carried out to filter the obtained hit compounds. A total of 125 compounds was finally selected based on the ranking order and visual examination. These compounds were further evaluated by a protein-based in vitro assay. Four compounds with new chemical scaffolds were identified to be hBRDT inhibitors. The most active of these compounds, T480, had a half maximal inhibitory concentration (IC50) of 9.02 µM. The detailed analysis of the binding mode of compound T480 provides important information for the further development of novel BRDT inhibitors.

Norartocarpetin, quercetin and naringenin were found to effectively inhibit 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) formation through trapping its phenylacetaldehyde and form their adducts in roast beef patties. Six adducts [8-C- or 6-C-(E-phenylethenyl) flavonoids] formed between phenylacetaldehyde and three flavonoids were detected in roast beef patties by UPLC-MS analyses and compared with their synthetic references. These flavonoid-phenylacetaldehyde adducts were synthesised and further subjected to cytotoxicity tests on three liver cancer cell lines HepG2, SMMC-7721 and QGY-7703. The adduct 8-C-(E-phenylethenyl)norartocarpetin (NARA1) was found to significantly induce cancer cell death with IC50 values about 7 μM. After pre-treating with MAPK and caspase inhibitors, alteration of the cell morphology and cleaved-PARP were detected in liver cancer cell lines administered with NARA1. These data indicated that norartocarpetin could inhibit PhIP formation in roast beef patties and form norartocarpetin-phenylacetaldehyde adducts. The adduct NARA1 has anticancer potential via intrinsic caspase-dependent and cell context-dependent MAPKs pathways.

Tubeimoside-1 (TBMS1) exerts its anticancer effects by inducing G2/M arrest and apoptosis of cancer cells. However, the precise molecular mechanism of its anti-tumor effects has not been fully elucidated, especially the signaling pathways involved in the early stage of TBMS1 stimulation. In this study, we employed stable isotope labeling by amino acids in cell culture (SILAC)-based quantitative proteomics approach and identified 439 proteins that exhibit significant differential expressions in NCI-H460 lung cancer cells upon exposure to TBMS1. Gene ontology and network analysis using DAVID and STRING on-line tools revealed that several nucleolar stress (ribosomal biogenesis) response proteins were differentially regulated by TBMS1. Functional validation demonstrated that TBMS1-induced NCI-H460 cell cytotoxicity involved nucleolar stress-induced p53/murine double minute clone 2 (MDM2), mTOR, and NF-κB signaling pathways.

The bioavailability and oxidative damage toxicity of lead (Pb) in seven food matrices, including rice, milk, tomato, garlic, apple, kelp and pork, were determined using an in vitro digestion/Caco-2 cell model and a rat pheochromocytoma (PC12) oxidative damage model. Results showed that Pb bioaccessibility and bioavailability in the apple and kelp groups were significantly lower than other food matrix groups, with corresponding values of 11.05-28.31% and 1.57-8.81%, respectively. Oxidative damage assays showed that digestion products of apple polyphenol extract, which was selected from seven food matrices, could increase the oxidation resistance and the levels of glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and acetyl cholinesterase (AChE) by 32.23%, 39.02%, 27.14% and 30.90%, respectively. Additionally, malondialdehyde (MDA) and reactive oxygen species (ROS) levels could be decreased by 59.66% and 40.21%, respectively. In conclusion, phenolics were an important food matrix that could decrease the bioavailability and oxidative damage of Pb.

Steroid-induced avascular necrosis of femoral head (SANFH) occurs frequently in patients receiving high-dose steroid treatment for these underlying diseases. The target of this study is to investigate the effect of microRNA-320 (miR-320) on SANFH by targeting CYP1A2. CYP1A2 expression was detected using immunohistochemistry. Specimens were collected from patients with SANFH and femoral neck fracture. Seventy rats were assigned into seven groups. The targeting relationship between miR-320 and CYP1A2 was verified by bioinformatics website and dual luciferase reporter gene assay. RT-qPCR and Western blot analysis were used to detect miR-320 and CYP1A2 expressions. The enzymatic activity of CYP1A2 was detected by fluorescence spectrophotometry. Hemorheology and microcirculation were measured in rats. MiR-320 expression decreased and CYP1A2 expression and enzymatic activity increased in SANFH patients compared to those with femoral neck fracture. CYP1A2 was the target gene of miR-320. Hemorheology and microcirculation results showed that up-regulated expression of CYP1A2 promoted the development of SANFH while increased expression of miR-320 inhibited the development of SANFH. Compared with the SANFH group, the SANFH + miR-320 mimic group showed increased miRNA-320 expression, and decreased CYP1A2 expression and enzymatic activity. Opposite results were found in the SANFH + miR-320 inhibitor group. The SANFH + miR-320 inhibitor + pCR-CYP1A2_KO group showed decreased miRNA-320 expression and the SANFH + pCR-CYP1A2_KO group showed decreased CYP1A2 expression and enzymatic activity. Our findings provide evidences that miR-320 might inhibit the development of SANFH by targeting CYP1A2.

Collagen α1 type XX, which contains fibronectin type III (FN3) repeats involving six FN3 domains (referred to as the FN#1–FN#6 domains), is an unusual member of the fibril-associated collagens with interrupted triple helices (FACIT) subfamily of collagens. The results of standard protein BLAST suggest that the FN3 repeats might contribute to collagen α1 type XX acting as a cytokine receptor. To date, solution NMR structures of the FN#3, FN#4 and FN#6 domains have been determined. To obtain further structural evidence to understand the relationship between the structure and function of the FN3 repeats from collagen α1 type XX, the crystal structure of the FN#2 domain from human collagen α1 type XX (residues Pro386–Pro466; referred to as FN2-HCXX) was solved at 2.5 Å resolution. The crystal structure of FN2-HCXX shows an immunoglobulin-like fold containing a β-sandwich structure, which is formed by a three-stranded β-sheet (β1, β2 and β5) packed onto a four-stranded β-sheet (β3, β4, β6 and β7). Two consensus domains, tencon and fibcon, are structural analogues of FN2-HCXX. Fn8, an FN3 domain from human oncofoetal fibronectin, is the closest structural analogue of FN2-HCXX derived from a naturally occurring sequence. Based solely on the structural similarity of FN2-HCXX to other FN3 domains, the detailed functions of FN2-HCXX and the FN3 repeats in collagen α1 type XX cannot be identified.

The purpose of this study was to investigate the effect of Huaier on autophagy of human hepatoma SK-HEP-1 cells and the effect of autophagy on the proliferation of SK-HEP-1 cells. CCK-8 assay was used to evaluate the effect of Huaier on the proliferation of SK-HEP-1 cells under different concentrations and different times. Acridine orange staining was used to measure the effect of Huaier on the autolysosome formation in SK-HEP-1 cells. Immunofluorescence assay was applied to examine the effect of Huaier on the expression and distribution of autophagy marker LC3 in SK-HEP-1 cells. In addition， LC3 expression was also checked by immunoblot analysis in the presence of Huaier. At last， the effects of Huaier in combination with autophagy inhibitor bafilomycin A1 on the proliferation of SK-HEP-1 cells was detected by CCK-8 assay. The results showed that Huaier aqueous extract significantly inhibited the proliferation of human hepatoma SK-HEP-1 cells in a dose- and time-dependent manner. Huaier aqueous extract dramatically promoted the formation of autolysosome in SK-HEP-1 cells. Moreover， Huaier markedly increased the number and intensity of intracellular LC3 fluorescent puncta and up-regulated LC3-Ⅱ expression. These data indicated that Huaier evidently activated autophagy of SK-HEP-1 cells. Additionally， autophagy inhibition significantly attenuated the sensitivity of SK-HEP-1 cells to Huaier treatment. Therefore， autophagy activation is involved in the inhibitory effects of Huaier on the proliferation of human hepatoma SK-HEP-1 cells.

Myeloid cell leukemia-1 (Mcl-1) has been a validated and attractive target for cancer therapy. Over-expression of Mcl-1 in many cancers allows cancer cells to evade apoptosis and contributes to the resistance to current chemotherapeutics. Here, we identified new Mcl-1 inhibitors using a multi-step virtual screening approach. First, based on two different ligand-receptor complexes, 20 pharmacophore models were established by simultaneously using 'Receptor-Ligand Pharmacophore Generation' method and manual build feature method, and then carefully validated by a test database. Then, pharmacophore-based virtual screening (PB-VS) could be performed by using the 20 pharmacophore models. In addition, docking study was used to predict the possible binding poses of compounds, and the docking parameters were optimized before performing docking-based virtual screening (DB-VS). Moreover, a 3D QSAR model was established by applying the 55 aligned Mcl-1 inhibitors. The 55 inhibitors sharing the same scaffold were docked into the Mcl-1 active site before alignment, then the inhibitors with possible binding conformations were aligned. For the training set, the 3D QSAR model gave a correlation coefficient r2 of 0.996; for the test set, the correlation coefficient r2 was 0.812. Therefore, the developed 3D QSAR model was a good model, which could be applied for carrying out 3D QSAR-based virtual screening (QSARD-VS). After the above three virtual screening methods orderly filtering, 23 potential inhibitors with novel scaffolds were identified. Furthermore, we have discussed in detail the mapping results of two potent compounds onto pharmacophore models, 3D QSAR model, and the interactions between the compounds and active site residues.

The Src homology 3 (SH3) domain is a small, noncatalytic domain with a conserved sequence of about 60 amino-acid residues that interacts with proline-rich peptides to form a protein complex. In this study, the C-terminal SH3 domain of human Tks4 (residues 853-911) was expressed, purified and crystallized. X-ray diffraction data were collected to 2.3 Å resolution. The crystal belonged to the trigonal space group P3121 (or P3221), with unit-cell parameters a = b = 83.87, c = 108.44 Å, α = β = 90, γ = 120°. Calculating the self-rotation and the native Patterson function did not lead to the detection of any noncrystallographic translational symmetry. Six, seven or eight protein molecules are likely to be present in the asymmetric unit, resulting in a Matthews coefficient and approximate solvent content of 2.71 Å(3) Da(-1) and 55%, 2.32 Å(3) Da(-1) and 47%, and 2.03 Å(3) Da(-1) and 39%, respectively. To solve the crystal structure of the C-terminal SH3 domain of human Tks4, the isomorphous replacement method is presently being utilized.

The aim of this study was to evaluate the diagnostic value of tests detecting antibodies against lipoarabinomannan (LAM), 38-kDa, and 16-kDa antigens for Mycobacterium tuberculosis (MTB). Sera from 160 tuberculosis (TB) patients and 150 non-TB healthy controls were subjected to simultaneous detection of antibodies against LAM, 38-kDa, and 16-kDa antigens using protein chips. The diagnostic value of the 3 TB antigens, alone or combined, was evaluated. Results showed that LAM and 38-kDa antigens had the highest positive rates in the TB patients. Tests showing any single positive antibody, 2 positive antibodies, and 3 positive antibodies had a sensitivity of 93.1%, 51.3%, and 15.6%, and a specificity of 81.3%, 96.6%, and 99.3%, respectively. The positive predictive value of tests showing any 2 positive antibodies and 3 positive antibodies was 94.2% and 96.1%, respectively. Combined detection of a selected panel of TB antibodies can improve the positive rates for TB diagnosis and can serve as an important aid to the diagnosis of TB especially extrapulmonary TB.

Inhibitors of transforming growth factor-beta Type I Receptor (ALK5) have been thought as potential drugs for the treatment of fibrosis and cancer and a considerable number of ALK5 inhibitors have been reported recently. In order to clarify the essential structure-activity relationship for the known ALK5 inhibitors as well as identify new lead compounds against ALK5, 3D pharmacophore models have been established based on the known ALK5 inhibitors. The best pharmacophore model, Hypo1, was used as a 3D search query to perform a virtual screening. The hit compounds were subsequently subjected to filtering by Lipinski's rule of five and docking studies to refine the retrieved hits. Finally a total of 100 compounds were obtained and some of them were selected for further in vitro and in vivo assay studies.

Two new ent-kaurane diterpenoids, dayecrystals D-E (1-2), together with nine known compounds, isojaponin A (3), rabdosin A (4), lushanrubescensin J (5), wikstroemioidin B (6), maoyecrystal C (7), rabdosin B (8), isodonal (9), shikokianin (10), and effusanin A (11), were isolated from the leaves of Isodon macrophyllus. The structures of the new compounds were elucidated using 1D and 2D NMR spectroscopy. The (13)C-NMR spectral data of compound 4 are reported for the first time. All of the compounds were tested for their cytotoxicities against DU145 and LoVo human tumor cells. Compounds 4, 10, and 11 showed inhibitory effects on DU145 cells with IC(50) values 5.90, 4.24, and 3.16 microM, and LoVo cells with IC(50) values 14.20, 17.55, and 3.02 microM, respectively.

Two new ent-kaurane diterpenoids, 6,20,15alpha-trihydroxy-6,7-seco-1alpha,7-olide-ent-kaur-16-ene (1) and 7beta,12alpha-dihydroxy-6beta,15beta-diacetoxy-7alpha,20-epoxy-ent-kaur-2,16-dien-1-one (2), together with the six known compounds, were isolated from the aerial part of Isodon nervosus. The structures of the new compounds were determined by spectral methods (1D, 2D NMR, and MS). Six compounds were assayed for their cytotoxicity against HL60, SMMC-7721, and HeLa human cell lines. Compounds 5, 7, and 8 showed significant cytotoxicity.

Many different microRNAs existed in nephrotic syndrome patients, and they may be involved in nephrotic syndrome occurrence. In order to further clarify miRNAs expression changes in nephrotic syndrome patients and their correlation with clinical features, this study investigated differential microRNA expression in the peripheral serum of patients with nephrotic syndrome and analyzed the correlation between miRNA with largest overexpression level and clinical features. miRNAs microarray was applied to screen different expressed miRNAs in nephrotic syndrome patients. Real-time PCR was performed to verify miRNA expression level. SPSS software was used to analyze correlation between miRNA expression and clinical features. Compared with healthy subjects, 35 miRNAs overexpressed and 24 miRNAs down-regulated in patients. After real-time PCR verification, 6 miRNAs up-regulated in nephrotic syndrome patients, including hsa-miR-181a, hsa-miR-210, hsa-miR-30a, hsa-miR-942, hsa-miR-192 and hsa-miR-586. miRNA-30a significantly overexpressed in nephrotic syndrome patients and with no difference between genders. miRNA-30a expression level in drug resistant nephrotic syndrome patients was obviously higher than the drug sensitive patients. miRNA-30a up-regulated most significantly in mesangial proliferative glomerulonephritis among different pathology types, while it decreased most obviously in glomerular lesions. miRNA differently expressed in the serum of nephrotic syndrome patients. miRNA-30a could be treated as the molecular marker in predict drug resistance and pathological type of nephrotic syndrome.

A novel ll,20: 1,20-diepoxy-ent-kaurane diterpenoid, maoyecrystal 1 (1), was isolated from Isodan japonicus, and its structure was elucidated by spectroscopic methods and comparison with another new ent-kauranoid, rubescensin W (2) from Isodon rubescens var. taihangensis. The structure of 2 was determined by single crystal X-ray diffraction analysis. A bioassay of their cytotoxity against K562 cells showed that the oxetane group of 1 might be a bioactive moiety.

Five new ent-kaurane diterpenoids, ludongnins F-J (1-5), along with 10 known compounds, guidongnins A-C (6-8), angustifolin (9), 6-epiangustifolin (10), sculponeatin J (11), gardenin D, 5,3',4'-trihydroxy-6,7,8-trimethoxyflavone, pedalitin, and quercetin, were isolated from the leaves of Isodon rubescens var. lushiensis. The structures of 1-5 were determined by spectroscopic analysis, as well as X-ray crystallographic analysis of 1. Compounds 1-11 were evaluated against K562 leukemia cells for their cytotoxic effects.

A new ent-kaurane diterpenoid maoyecrystal F (1) and its acetonide derivative (2), together with seven known compounds, lasiodonin, maoyerabdosin, odonicin, enmenin, oridonin, beta-sitosterol and daucosterol, were isolated from the leaves of Isodon japonica. (C) 2003 Elsevier Science B.V. All rights reserved.

The presence of a septum in the first extensor compartment is closely associated with the pathophysiology of de Quervain disease, and affects the efficacy of corticosteroid injection and surgical release. This study aimed to examine the incidence and length of the first extensor compartment septum. Forty sides of the wrists in 20 cadavers were used. The presence of a septum in the first extensor compartment was examined. The septum length was recorded with the radial styloid process as the reference point. The anatomical variations of the first extensor compartment were classified into 3 types. Type I compartment was found in 7 sides in males (29.2%) versus 6 sides in females (37.5%, P = .733), type II was found in 6 sides in males (25%) versus 1 side in females (6.25%, P = .21), and type III was found in 11 sides in males (45.8%) versus 9 sides in females (56.25%, P = .56). There was no significant difference in the septum length between males and females (5.3 ± 2.3 vs 4.8 ± 1.1 mm, P = .54). The incidence of a septum in the first extensor compartment is approximately 50%. The mean septum length is 5 mm. Injection at 5 mm proximal to the radial styloid process has a great chance of delivering the steroids into both subcompartments. Exposure to 5 mm proximal to the radial styloid process can avoid the overlook of subcompartment and achieve adequate decompression of the first extensor compartment.

To explore the influence factors of salt-sensitive hypertension and to observe changes of blood pressures and urinary sodium and potassium excretion in response to acute oral saline loading among essential hypertensive patients in China.Essential hypertensive patients from Beijing Jinzhan second community were included in this study. Salt-sensitivity was determined via the improved Sullivan's acute oral saline loading and furosemide volume-depletion tests. Binary logistic regression analysis was applied to explore influence factors of salt-sensitive hypertension. Acute oral saline loading induced changes on blood pressures and urinary sodium and potassium excretion were observed.Sixty-three salt-sensitive hypertensive patients were classified out of a total of 342(18.4%) essential hypertensive patients. Salt-sensitive patients were elder than the non-salt-sensitive patients (P0.05) . Binary logistic regression analysis showed that age (OR = 1.744, 95%CI:0.922-3.300, P0.05) , gender (OR = 0.728, 95%CI:0.374-1.415, P0.05) , total cholesterol level (OR = 1.168, 95%CI:0.882-1.547, P0.05) and 24-hour urinary sodium (OR = 0.998, 95%CI:0.995-1.002, P0.05) were not influencing factors of salt-sensitivity among essential hypertensive patients. Bivariate general linear models for repeated measures showed that there were significant statistical differences on blood pressures and urinary electrolytes concentrations between the beginning of trials, 2 hours after acute saline loading and 2 hours after furosemide volume-depletion(all P0.01). There was a greater blood pressures change in salt-sensitive patients than in non-salt-sensitive patients(all P0.01) while urinary electrolytes concentrations change was similar between two groups(all P0.05).Age, gender, total cholesterol level and 24-hour urinary sodium are not influencing factors of salt-sensitivity among essential hypertensive patients in this study. Impaired pressure natriuresis during acute oral saline loading and furosemide volume-depletion tests is presented in salt-sensitive essential hypertensive patients.

Background: DNA repair gene polymorphisms can contribute to susceptibility of human cancer, including gastric cancer. Three single nucleotide polymorphisms (SNPs) of xeroderma pigmentosum group D (XPD) and X-ray repair cross complement 1 (XRCC1) genes were genotyped in gastric cancer and control subjects in a population from Southwestern China for their association with susceptibility of gastric cancer risk. Methods: 190 hospital-based cases and 180 matched controls were recruited and blood samples were collected from each of them and amplified with a PCR and DNA sequenced for XPD Asp312Asn, XRCC1 Arg194Trp, and XRCC1 Arg280Gln genotyping. Results: Allelic association analysis of these three SNPs showed that the frequency of XRCC1 194Trp in gastric cancer case and the control was 17.2% and 7.3%, respectively, which was significantly associated with gastric cancer risk (OR = 2.72, 95% CI: 1.04–7.24, p = 0.027). Furthermore, XRCC1 194Trp allele increased gastric carcinoma risk in male patients with older age and distant metastasis of gastric cancer. In addition, XRCC1 Trp allele but not XRCC1 Arg allele was closely associated to development of gastric cardia carcinoma. However, other SNPs did not show an association with gastric cancer risk or other clinicopathologic data of the patients. Conclusion: XRCC1 194Trp allele significantly increased the risk of gastric cancer and also associated with risk of gastric cardia carcinoma and promoted distant metastasis of gastric cancer. Future study will verify these findings for use of this SNP as biomarker in gastric cancer.

This study was purposed to investigate the megakaryocytic dysplasia and leukemia-associated phenotypes (LAP) of acute myeloid leukemia (AML) in the elderly. The megakaryocytic dysplasia, lineage infidelity, asynchronous antigen expression, total WBC count, and karyotypes were observed in the 147 none M(3)-AML patients. Logistic regression were used to analyzed the difference between the elderly (ageor = 60) and the control. The results showed that out of the total 147 patients (66 elderly patients, and 81 younger patients) 124 patients accepted induction chemotherapy, in which 70 cases achieved complete remission (elderly 18, younger 52, p = 0.008); megakaryocytic dysplasia was found in 32 patients (21.8%); CD33 and CD19/CD7 (lineage infidelity) was co-expressed in 55 patients (37.4%), CD34 and CD11b (asynchronous antigen expression) was co-expressed in 65 patients (44.2%); white blood cell count25 x 10(9)/L was found in 52 patients (35.4%). By the Logistic regression, compared with the control, in the elderly patients there was difference in the megakaryocytic dysplasia, and the co-expression of CD33/CD19/CD7 and CD34/CD11b (OR = 4.315, 2.761, 0.397; p = 0.001, 0.006, 0.020), but there was no difference in the total WBC count and karyotypes (OR = 0.802, 1.096; p = 0.646, 0.813). It is concluded that the incidence of megakaryocytic dysplasia, such as lineage infidelity, and asynchronous antigen expression, in elderly patients is higher than that in younger patients.

To develop and optimize real-time fluorescence quantitative PCR (FQ-PCR) with the housekeeping gene RAG2 as cell number control to quantify T-cell receptor excision circle (TREC) in the peripheral blood.The real-time PCR system for amplifying TREC and RAG2 genes was established on the basis of ABI 7000 apparatus using Golden Taq system, designed primers, TaqMan-MGB probes and optimized buffer. PCR conditions were optimized with standard samples of TREC plasmid.The amplification with the primer pair T(3) and T(4) was more efficient than that with T(1) and T(2). More specific and efficient amplification in FQ-PCR was achieved using TaqMan-MGB probes as compared with general Taq-Man probes. Golden Taq was more effective than general Taq in improving the specificity and decreasing the artifact, and 95 degrees C; for 10 min, 95 degrees C; for 5 s, and 53 degrees C; for 30 s for a total of 40 cycles using ABI7000 was found as the optimized thermal parameter setting.An optimized real-time PCR protocol for detecting TREC in peripheral blood mononuclear cells is established.

To study the inhibition of the expression of bcl-xL gene induced by RNA interference in CNE-2Z cell line in addition to the inhibition of its proliferation and apoptotic induction.Small interfering RNAs targeting bcl-xL gene were synthesized by using web design software provided by Amnion and the silencer short interfering RNA (siRNA) construction kit; fluorescein-labeled siRNAs were done by FAM-silencer siRNA labeling kit; siRNAs were transfected into CNE-2Z cells by using lipofectamine 2000 reagent; siRNA transfection efficiencies were analyzed by fluorescent microscopy; down-regulation of bcl-xL was detected by RT-PCR; thiazolyl blue (MTT) assay was used to assess the cell growth; apoptosis of CNE-2Z cells was analyzed by flow cytometry.Green fluorescence in the cells was seen clearly in FAM-labeled siRNA transfected group under the fluorescent microscope while none in the untransfected group. Different down-regulations of bcl-xL mRNA expression were found in the transfected groups. The expression of bcl-xL mRNA decreased by 10% - 70% in the siRNAs transfected CNE-2Z by RT-PCR scan analysis. The inhibitory rate of cell proliferation depended on time and concentrations to some extent. Different cell apoptosis could be induced by different concentrations of siRNA4.The synthesized siRNAs in vitro were able to down-regulate the expression of bcl-xL There were different capabilities of the specific siRNAs down-regulation. The transient transfected bcl-xL siRNA4 could effectively inhibit the growth of the cancer cells and induce theirs apoptosis. It was suggested that the siRNA technique provide not only an extremely powerful tool for the functional analysis of genome but also a new method for anti-nasopharyngeal carcinoma gene therapy.

To investigate the alteration of peripheral blood naive T cells in adult patients after hematopoietic stem cell transplantation (HSCT).Peripheral blood samples were collected from 49 patients requiring stem cell transplantation before and 15, 30, 90, and 180 d after transplantation, respectively. Dynamic changes of CD4(+)CD45RA(+)/CD8(+)CD45RA(+) cell counting were measured using flow cytometry.Flow cytometry results of 90 samples showed that CD8(+)CD45RA(+) cells recovered to normal level 30 d after transplantation, whereas CD4(+)CD45RA(+) cells remained low and kept a slow pace of gradual increase over the 6 months following the transplantation. More rapid recovery of the transport and regeneration function of the thymus cells was achieved in patients receiving hematopoietic stem cell autotransplant than in those with allotransplant.Measurement of the changes of CD4(+)CD45RA(+)/CD8(+)CD45RA(+) cell ratio using flow cytometry may provide insights into the molecular picture of the thymus regeneration function in association with immune reconstruction process in patients after stem cell transplantation. The number of newly generated T cells transported from the thymus can be a putative marker of immune reconstruction after transplantation.